This invention relates to a process for the synthesis and method of use of an effective amount of a creatine heterocyclic acid salt for the regulation athletic function in humans. Creatine synthesis traditionally has utilized many forms ranging from free acid, salt, ester, amide, and hydrates. Creatine hydrates have been the preferred form, which may consist of a monohydrate salt, a dihydrate salt, a trihydrate salt, and a tetrahydrate salt. This is most likely due to the fact that the hydrate salts are thought to produce the most water soluble forms thereby possessing the most orally bioavailable forms. Although we purpose for the first time that the process for the synthesis and use of a creatine heterocyclic acid salt is novel, unobvious, and superior due to enhanced absorption, bioavailability and function.
Creatine is a nitrogenous organic acid that is found in muscle and nerve tissue. The body forms creatine from the amino acids arginine, glycine and methionine. Creatine is stored intramuscularly as creatine phosphate (phosphocreatine). Phosphocreatine donates its phosphate to adenosine diphosphate (ADP) to make adenosine triphosphate (ATP) and thus increases the rate of ATP regeneration, which promotes enhanced strength and endurance. Creatine is also thought to promote muscle mass via increasing the intracellular concentration of water, which is thought to activate protein synthesis and thus contribute to increases in strength, endurance and recovery.
Creatine has been patented for number of applications. For instance, U.S. Pat. No. 5,925,378 by Carnazzo demonstrates a method for enhancing delivery and uniformity of concentration of cellular creatine. U.S. Pat. No. 5,973,199 by Negrisoli et al. describes hydrosoluble organic salts of creatine. U.S. Pat. No. 6,172,111 by Pischel et al. demonstrates a method for producing creatine pyruvates. U.S. Pat. No. 6,114,379 by Wheelwright et al. further demonstrates a process for bioavailable chelates of creatine and essential metals. More recently U.S. Pat. No. 6,211,407 by Thomson describes a process for dicreatine citrate and tricreatine citrate and method of making same.
Creatine has been successfully utilized in a number of applications that either improve oral bioavailability or enhance function. While it is accepted that any improvement in creatine absorption should lead to enhanced creatine function, it is not equivalent to simultaneously improving creatine absorption while providing a synergistic compound that provides ergogenic benefit and acts as a functional salt carrier. The creatine heterocyclic acid salt may consist of a mono, di, or tri creatine orotate or derivative thereof. These novel and unobvious combinations provide a simultaneous synergistic action due to the use of mono, di and tricreatine cations, which are molecularly bonded to various forms of orotic acid, which in turn provide ergogenic functions while acting as efficient water soluble carriers or transporters. It should be understood that this invention is not construed as limited in scope by the details contained therein, as it is apparent to those skilled in the art that modification in materials and methods can be made without deviating from the scope of the invention.
Orotic acid (1,2,3,6-Tetrahydro-2,6-dioxo-4-pyrimidecarboxylic acid) is a heterocyclic organic acid that is a precursor of pyrimidine and therefore, has an influence on the metabolism of the nucleic acid. Orotic acid is also an intermediate in the manufacture of the pyrimidine bases such as uracil, cytosine, and thymine. Orotic acid at one time was classified as vitamin B 13, which was found to have growth-promoting and vitamin-like properties when added to the diets of laboratory animals as described by Rundles et al. Blood. 1958;13(2):99-115 and Moruzzi et al. Biochem Z. 1960;333:318-27. Orotic acid also provides an additional ergogenic benefit due to its role in the formation of uridine diphoshate (UDP) glucose, which is high energy form of glucose and a precursor to glycogen or the storage form of glucose. While orotic acid has been shown as a growth promoter and ergogenic aid it also has been shown to form stable water soluble electrostatic bonds with various minerals and vitamins such as magnesium orotate, calcium orotate, and vitamin E orotate as described in U.S. Pat. No. 3,944,550.
U.S. Pat. No. 5,973,199 by Negrisoli describes a method for producing stable hydrosoluble organic salts of creatine. Negrisoli states that the low water solubility of creatine dictates high oral doses for adequate creatine absorption. Negrisoli discloses a process for the synthesis of creatine citrate, maleate, fumarate, tartrate or malate anions. This combination produces higher water solubility from 3 to 15 times higher then that of creatine itself. This invention represents an improvement in standard creatine preparations due to the combination of creatine and the previously mentioned anions. However this combination only improves creatine absorption, which may lead to enhanced creatine function if adequate creatine storage occurs in the muscle cell. It does not provide a salt that simultaneously increases creatine absorption and provides a synergistic ergogenic effect to compliment the actions of creatine.
U.S. Pat. No. 6,172,111 by Pischel et al. demonstrates a method for producing creatine pyruvates. This combination is described to be physiologically safe, having a long shelf life, being highly soluble in water and having good bioavailability. Pischel discloses that creatine pyruvate may be of benefit for treating conditions of oxygen deficit (ischemia), overweight or obesity, preventing the formation of free radicals and scavenge free radicals or oxidizing species of oxygen, and enhancing long-term performance. This invention represents an improvement in standard creatine preparations due to the combination of creatine and pyruvate. However this combination only attempts to provide a long-term synergistic ergogenic benefit due to the ability of pyruvate to contribute to fat loss when administered in large doses. This combination can not provide acute or immediate synergistic ergogenic benefit, which is supported by research by Stone, et al. Int J Sport Nutr 1999 Jun;9(2):146-65, which demonstrates that pyruvate alone imparts no ergogenic benefit, which leads to the fact that the creatine portion is providing the only acute ergogenic benefit.
U.S. Pat. No. 6,114,379 by Wheelwright et al. demonstrates a process for bioavailable chelates of creatine and essential metals. Wheelwright states that it would be desirable to provide a creatine chelate for oral consumption comprised in such a way that the creatine ligand is protected by the metal from undergoing cyclization in the acidic environment of the stomach, thus making the creatine more readily available to the body in a useful form. This combination is described to enhance fatigue resistance and recovery time during high intensity, short-term exercise by providing a nutrient formulation, which is comprised of the anabolic nutrients phosphorus and creatine, which are precursors for the body's formation of phosphocreatine. It is also described to complement creatine and phosphorus with chelated magnesium as an activator of the enzymes that hydrolyze and transfer phosphate groups, e.g. the phosphatases and those concerned in the reactions involving adenosine triphosphate (ATP). This invention represents an improvement in standard creatine preparations due to the combination of creatine and mineral chelates. However this combination only improves creatine absorption, which may lead to enhanced creatine function if adequate creatine storage occurs in the muscle cell. It does not provide a salt that simultaneously increases creatine absorption and provides a synergistic ergogenic effect to compliment the actions of creatine. It is well known by those skilled in the art that minerals do not provide ergogenic benefit in healthy fed individuals but may provide benefit to those who are deficient in said minerals.
U.S. Pat. No. 6,211,407 by Thomson describes a process for dicreatine citrate and tricreatine citrate and method of making same. Thompson states that it would be desirable to provide another form of creatine that is stable, and that can prevent or impede the conversion of creatine to creatinine. It would further be desirable to provide a form of creatine salt that is other than a monocreatine citrate form of the salt. This invention represents an improvement in standard creatine preparations due to the combination of dicreatine/tricreatine and citrate. However this combination only improves creatine absorption, which may lead to enhanced creatine function if adequate creatine storage occurs in the muscle cell. It does not provide a salt that simultaneously increases creatine absorption and provides a synergistic ergogenic effect to compliment the actions of creatine.